Nitrates

Question 1

How do nitrates work?

Answer 1

They undergo denitration in the bloodstream to release NO, a short lived gas which can travel across cellular membranes. NO activates guanylate cyclase and elevates intracellular cyclic GMP in the vasculature smooth muscle cell producing relaxation of vascular (and other) smooth muscle and produces veno- and vasodilation and coronary vasodilation

Question 2

Endogenous NO produced by nitric oxide synthase in our endothelial cells is the most important vasodilation pathway we have and it tends to decrease with age

Answer 2

Endogenous NO produced by nitric oxide synthase in our endothelial cells is the most important vasodilation pathway we have and it tends to decrease with age

Question 3

CV effects of nitrates?

Answer 3

• venodilation decreases preload (only one)

- coronary vasodilation (can prevent or reverse coronary vasospasm)

Question 4

Overall effect of nitrates on hemodynamics at usual doses?

Answer 4

very transient effects

BP unchanged or slight decrease

HR unchanged or slight increase

PVR decreased

CO reduced (slight)

Question 5

Adverse effects of nitrates.

Answer 5

seen mostly with higher doses:

• hypotension via arterial vasodilation
• transient headache due to vasodilation of meningeal arteries
• drug rash in cutaneous nitrates and long acting

Question 6

Effect of hypotension via arterial vasodilation caused by nitrates?

Answer 6

reflex tachycardia and increased contraction

Question 7

What is a very important potential interaction of nitrates?

Answer 7

Viagra uses Type V PDE inhibitors which prevent breakdown of cGMP and nitrates stimulate synthesis of cGMP which could cause a compounding effect that causes profound hypotension and possible induce myocardial ischemia

Question 8

What is major problem with nitrate therapy?

Answer 8

tolerance leading to loss of efficacy

Question 9

What is the recommended course of use of nitrates?

Answer 9

create periods of 8-12hr “nitrate free” intervals each day, usually at night

Question 10

What are some methods of tolerance to nitrates?

Answer 10

• volume expansion
• reflexive neurohumoral activation
• depletion of tissue cysteine stores

Question 11

Describe how depletion of tissue cysteine stores causes tolerance to nitrates?

Answer 11

cysteine is needed in the processing of nitrate to NO into the body

Question 12

What is anginal rebound?

Answer 12

when IV nitroglycerin is removed in unstable angina, a coronary vasospasm can develop. Thus, overlap with transdermal or oral forms